title: Infusion of a glucose solution reduces autophagy in the liver after LPS-induced systemic inflammation.
abstract: Autophagy is a natural process by which a cell maintains homeostasis, usually taking place unnoticed by adjacent cells. Glucose is involved in a negative feedback loop in autophagy. Autophagy is characterized by the induction and secretion of HMGB1, yet the nature of the inflammatory response during and the effect of glucose administration on autophagy are not well understood. Systemic inflammation was induced in experimental animals by LPS injection (7.5 mg/kg) followed by a continuous infusion of either 1%, 5%, or 25% glucose. Autophagy was visualized by immunohistochemistry 12 h after LPS injection. Likewise, protein levels of microtubule-associated protein light chain 3 (LC3)-II, autophagy-related protein 7 (Atg7), and high-mobility group box 1 (HMGB1) were assayed by western blot analysis. We found that autophagy increased in liver tissue in response to LPS-induced systemic inflammation. However, protein levels decreased in rats receiving LPS and a 5% glucose solution. Our results suggest that LPS-induced systemic inflammation increases autophagy in liver cells, potentially involving the upregulation of LC3-II, Atg7, and HMGB1. We also show that a 5% glucose infusion reduces autophagy. We propose that maintaining serum glucose levels with an adequate glucose dose improves systemic inflammation by reducing autophagy.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Oita University Faculty of Medicine, 1-1 Idaigaoka-Hasamamachi, Yufu City, Oita, 879-5593, Japan. saku@med.oita-u.ac.jp
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hagiwara
authors.forename: Hideo
authors.initials: H
authors.lastname: Iwasaka
authors.forename: Akira
authors.initials: A
authors.lastname: Hasegawa
authors.forename: Kyousuke
authors.initials: K
authors.lastname: Kudo
authors.forename: Jyunya
authors.initials: J
authors.lastname: Kusaka
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Oyama
authors.forename: Takayuki
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001343:Autophagy / Q000187:drug effects*; D000071193:Autophagy-Related Protein 7; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D024243:HMGB1 Protein / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism
chemical_list: C561242:Atg7 protein, rat; D001786:Blood Glucose; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes; D005947:Glucose